Antibacterial, Antibiofilm, and Anti-inflammatory Effects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights into Underlying Mechanisms

IF 5.3 2区材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Nano Materials Pub Date : 2024-10-30 DOI:10.1021/acs.jmedchem.4c02157

S. Dinesh Kumar, Jin Kyeong Lee, Naveen Kumar Radhakrishnan, Jeong Kyu Bang, Byeongkwon Kim, Shubhash Chandra Chaudhary, Ajish Chelladurai, Byambasuren Ganbaatar, Eun Young Kim, Chul Won Lee, Sungtae Yang, Yangmee Kim, Song Yub Shin

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引用次数: 0

Abstract

We developed two short helical antimicrobial peptides, HVF18-a3 and its d-enantiomer, HVF18-a3-d, derived from the thrombin C-terminal peptide HVF18. These peptides exhibit potent antimicrobial activity against various bacteria by compromising both the outer and inner membranes, with low hemolytic activity. They are stable in the presence of physiological salts and human serum, exhibiting a low potential for developing drug resistance and excellent antibiofilm activity against Gram-negative bacteria. HVF18-a3-d also neutralized lipopolysaccharide (LPS) through direct binding interactions and suppressed the production of inflammatory cytokines through the inflammatory signaling pathway mediated by Toll-like receptor 4 in RAW264.7 cells stimulated with LPS. Both pre- and post-treatment with HVF18-a3-d significantly protected mice against fatal septic shock induced by carbapenem resistant Acinetobacter baumannii. These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates for developing antibiotics against Gram-negative sepsis.

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一种新型凝血酶生成肽在败血症模型中的抗菌、抗生物膜和抗炎作用：揭示内在机制

我们开发了两种短螺旋抗菌肽，即 HVF18-a3 及其 d-对映体 HVF18-a3-d，它们来自凝血酶 C 端肽 HVF18。这些肽能破坏细菌的外膜和内膜，对各种细菌具有很强的抗菌活性，而且溶血活性很低。它们在生理盐和人体血清中稳定，产生耐药性的可能性较低，对革兰氏阴性菌具有出色的抗生物膜活性。HVF18-a3-d 还能通过直接结合相互作用中和脂多糖（LPS），并通过 Toll 样受体 4 介导的炎症信号通路抑制受 LPS 刺激的 RAW264.7 细胞中炎性细胞因子的产生。在耐碳青霉烯鲍曼不动杆菌诱导的致命性脓毒性休克中，HVF18-a3-d 治疗前后均能显著保护小鼠。这些研究结果表明，HVF18-a3 和 HVF18-a3-d 是开发抗革兰氏阴性败血症抗生素的理想候选药物。

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来源期刊

ACS Applied Nano Materials Multiple-

CiteScore

8.30

自引率

3.40%

发文量

1601

期刊介绍： ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.